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Secrets of Telomerase Revealed

Researchers unlock active region of enzyme involved in cancer, aging

MONDAY, Sept. 1 (HealthDay News) -- Researchers have revealed the structure of the active region of telomerase, an enzyme involved in both cancer and aging.

Telomerase works by adding repeats of a short DNA sequence to the ends of chromosomes -- known as telomeres -- to prevent damage and loss of genetic information during cell division. Telomerase works in embryonic stem cells and other cells that multiply frequently, but is switched off almost entirely in normal adult cells to prevent the dangers of runaway proliferation.

In cancer cells, the ability to activate telomerase is often regained. Telomerase has been implicated in 90 percent of human tumors.

Because of this, telomerase is widely considered the number one target for the development of new cancer treatments. But until now, the enzyme's structure has been in large part a mystery.

"Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells," study author Emmanuel Skordalakes, an assistant professor in The Wistar Institute's Gene Expression and Regulation Program, said in a news release from the institute.

In addition to telomerase's role in cancer, it also plays a part in aging. When telomerase is dormant, as it is in most normal adult cells, cells eventually become unstable and die. But when telomerase is active, cells continue living and dividing. This is why scientists believe that preserving telomerase under controlled conditions could possibly lead to new anti-aging therapies.

In their study, which was published in the Aug. 31 issue of Nature, Skordalakes and his colleagues found that they could use a gene from the red flour beetle to produce large amounts of telomerase in a stable form for study.

"That was really the breakthrough," said Skordalakes. "Once we found that the gene from this organism expressed the protein in the quantities we needed, we were able to move quickly."

Using X-ray crystallography, the researchers were then able to determine the three-dimensional structure of telomerase's active region.

"It's extremely exciting," said Skordalakes. "For the first time, we can see how telomerase assembles at the end of chromosomes to initiate telomere replication."

Skordalakes plans to further investigate the active region of telomerase and search for new potential cancer therapies.

More information

The American Cancer Society has more about cancer.

--Krisha McCoy

SOURCE: The Wistar Institute, news release, Aug. 31, 2008

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